Management of Neutropenia in Ph+-CML Patient on Dasatinib
The patient should continue Sprycel (dasatinib) 100mg daily as the current ANC of 1.42 × 10^9/L is above the threshold requiring dose modification. 1, 2
Assessment of Current Neutropenia
The patient presents with:
- Ph+-CML on Sprycel 100mg
- History of neutropenia requiring 1-month hold
- Current WBC of 3.4 and ANC of 1.42 × 10^9/L
- Two previous CBCs without significant improvement
Dasatinib Dose Modification Guidelines for Neutropenia
According to European LeukemiaNet and FDA guidelines, dasatinib dose modifications are only required when:
- ANC falls below 0.5 × 10^9/L (severe neutropenia) 1
- For chronic phase CML patients, dasatinib should be held until ANC ≥ 1.0 × 10^9/L 2
The patient's current ANC of 1.42 × 10^9/L is above these thresholds, allowing for continuation of the full dose.
Management Algorithm
Continue dasatinib 100mg daily
- Current ANC (1.42 × 10^9/L) is above the threshold requiring dose modification
- Monitor CBC weekly for the next 4-6 weeks 1
If ANC drops below 0.5 × 10^9/L:
- Hold dasatinib until ANC ≥ 1.0 × 10^9/L
- Resume at original starting dose if recovery occurs within 7 days
- If recovery takes longer than 7 days, reduce to 80mg daily 2
If recurrent neutropenia occurs:
- For second episode: reduce to 80mg daily
- For third episode: further reduce to 50mg daily 2
Monitoring Recommendations
- Weekly CBC monitoring for the next 4-6 weeks 1
- After stabilization, monitor CBC every 2 weeks until month 3
- After month 3, monitor every 3 months if stable 1
- Evaluate BCR-ABL transcript levels every 3 months to assess treatment response 1
Important Considerations
Cause of neutropenia: Consider bone marrow aspiration or biopsy if neutropenia persists or worsens to determine if it's related to leukemia or medication 1, 2
Growth factors: Growth factors (G-CSF) can be used in combination with dasatinib for patients with resistant neutropenia 1
Treatment response: Continue to monitor BCR-ABL transcript levels to ensure adequate response to therapy despite the neutropenia 1
Caveats and Pitfalls
Don't reduce dose prematurely: Reducing dasatinib dose when ANC is above threshold may compromise treatment efficacy
Monitor for other side effects: Watch for pleural effusion, which is common with dasatinib but less frequent in the 100mg once-daily regimen 3
Drug interactions: Avoid strong CYP3A4 inhibitors/inducers that may affect dasatinib levels 1
Long-term implications: Persistent cytopenias may be associated with worse outcomes, so continued monitoring is essential 1